The prevalence of microalbuminuria and relevant cardiovascular risk factors in Turkish hypertensive patients

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The prevalence of microalbuminuria and relevant cardiovascular

risk factors in Turkish hypertensive patients

Türk hipertansiyon hastalarında mikroalbuminüri sıklığı ve

ilişkili kardiyovasküler risk faktörleri

Ömer Kozan, M.D.,

#

Emin Evren Özcan, M.D.,

Oktay Sancaktar, M.D.,

§

Giray Kabakcı, M.D.,

and the Turkish investigators of the i-SEARCH study

+

Cardiology Departments of, #Medicine Faculty of Dokuz Eylül University, İzmir; İzmir Hospital, İzmir; §İstanbul Şafak Hospital, İstanbul; Medicine Faculty of Hacettepe University, Ankara

+Complete list of the investigators and their affiliations are given in the Appendix

Received: December 24, 2010 Accepted: August 23, 2011

Correspondence: Dr. Ömer Kozan. Dokuz Eylül Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, 35340 İnciraltı, İzmir, Turkey. Tel: +90 232 - 464 63 08 e-mail: omer.kozan@deu.edu.tr

© 2011 Turkish Society of Cardiology

Amaç: Mikroalbuminürinin (MAU) hipertansiyon hasta-larında kardiyovasküler riskin önemli bir öngördürücüsü olduğu yolunda gittikçe artan veri bulunmaktadır. Bu ça-lışma, ayaktan takip edilen hipertansif hastalarda MAU sıklığının ve ilgili kardiyovasküler risk faktörlerinin tanım-lanması amacıyla tasarlandı.

Çalışma planı: Dünya çapında 26 ülkeden 1750 merke-zin katılımı ile yürütülen çokuluslu i-SEARCH çalışma-sının Türkiye kolunu temsil eden gözlemsel, kesitsel ve çokmerkezli bu çalışmaya Türkiye’den toplam 1926 hi-pertansiyon hastası alındı. Yalancı pozitif MAU testine yol açacak nedenlere sahip hastalar çalışmaya alınmadı. Mikroalbuminüri sıklığı “dipstick” testi ile belirlendi; ayrıca, çalışma grubunda eşlik eden hastalıklar, kullanılan ilaçlar ve kardiyovasküler risk faktörleri soruşturuldu.

Bulgular: Mikroalbuminüri sıklığı %64.7 bulunurken, cinsiye-te göre farklılık gözlenmedi. Hastaların büyük çoğunluğunda (%82.5) kontrolsüz hipertansiyon, %35.6’sında dislipidemi, %35.5’inde tip 2 ağırlıklı olmak üzere diyabet saptandı. Has-taların yaklaşık üçte birinde (%26.4) kardiyovasküler risk ile ilişkili komorbidite, %20.3’ünde koroner arter hastalığı (KAH) vardı. Hastaların tamamına yakınında (%96.8), hipertansiyo-na ek olarak bir veya daha çok sayıda kardiyovasküler risk faktörü (miyokart enfarktüsü veya KAH için aile öyküsü, diya-bet, dislipidemi, fiziksel egzersiz eksikliği ve sigara içme) bu-lunmaktaydı. Koroner arter hastalığı varlığında daha yüksek MAU değerlerine doğru bir eğilim gözlendi.

Sonuç: Mikroalbuminüri testleri, hipertansiyon hasta-larında gelişebilecek olan kardiyovasküler morbidite ve mortaliteyi değerlendirmede rutin olarak kullanılabilecek tarama ve izleme aracıdır.

Objectives: A growing body of data illustrates the impor-tance of microalbuminuria (MAU) as a strong predictor of cardiovascular risk in the hypertensive population. The present study was designed to define the prevalence of MAU and associated cardiovascular risk factors among Turkish hypertensive outpatients.

Study design: Representing the Turkish arm of the

multi-national i-SEARCH study involving 1,750 sites in 26 coun-tries around the world, a total of 1,926 hypertensive patients from different centers were included in this observational and cross-sectional survey study. Patients with reasons for a false-positive MAU test were excluded. The prevalence of MAU was assessed using a dipstick test, and patients were inquired about comorbidities, comedication, and known cardiovascular risk factors.

Results: The overall prevalence of MAU was 64.7% and

there was no difference between genders. Most of the pa-tients (82.5%) had uncontrolled hypertension, 35.6% had dyslipidemia, and 35.5% had diabetes, predominantly type 2. Almost one-third of the patients (26.4%) had at least one cardiovascular-related comorbidity, with 20.3% having doc-umented coronary artery disease (CAD). Almost all patients (96.8%) had one or more risk factors for cardiovascular dis-ease in addition to hypertension, including family history of myocardial infarction or CAD, diabetes, dyslipidemia, lack of physical exercise, and smoking. A trend towards higher MAU values in the presence of CAD was determined.

Conclusion: Microalbuminuria tests should be routinely used as a screening and monitoring tool for the assess-ment of subsequent cardiovascular morbidity and mortal-ity among hypertensive patients.

ÖZET

ABSTRACT

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M

icroalbuminuria, subclinical increase in urinary

albumin excretion rate of 30-300 mg/day in a

random urine spot check,

[1]

has been considered to be

an independent risk factor for morbidity and mortality

related to cardiovascular disease and nephropathy not

only in diabetic populations

[2]

but also in nondiabetic

hypertensives,

[3]

as well as among nondiabetic and

nonhypertensive general population.

[4,5]

Microalbuminuria is considered to be a measure

of generalized vascular leakiness for albumin

[6]

sec-ondary to endothelial dysfunction.

[7]

It is known to

be an integrated marker of structural and functional

abnormalities in hypertension, such as hypertensive

cardiovascular abnormalities, renal and endothelial

dysfunction,

[8]

suggesting a common

pathophysiolo-gy

[9]

for coronary vasomotor abnormalities and MAU.

Therefore, MAU has been considered to be the major

independent determinant of ischemic heart disease

among hypertensive patients.

[10]

In this context, reduction in the MAU rate has

been reported to correspond to a reduction in

cardio-vascular events and mortality in hypertensive patients,

particularly when renin-angiotensin system-blocking

drugs are used in their treatment.

[8,11]

Hence, a retrospective analysis of data from the

LIFE study showed that a reduction in MAU was

as-sociated with a significantly reduced risk for

nonfa-tal myocardial infarction, stroke, and cardiovascular

death.

[8]

Accordingly, the magnitude of decreases in

albuminuria achieved with renin-angiotensin system

intervention was reported to be related not only to the

degree of renal protection, but also to the degree of

reduction in cardiovascular risk among type 2 diabetic

patients with diabetic nephropathy,

[12]

and also among

those with nondiabetic renal disease.

[13]

Despite numerous trials demonstrating the

bene-fits of lowering high blood pressure among

hyperten-sive patients,

[14]

available data suggest that the rates of

treatment and control remain suboptimal,

[14,15]

which

increases the likelihood of cardiovascular

complica-tions. Since the level of albuminuria has been closely

related to the risk level during antihypertensive

treat-ment, alterations in albuminuria seem to reflect the

risk factor status if routinely screened in

hyperten-sive patients.

[8]

While such a screening for MAU is

recommended in international treatment guidelines

for hypertensive patients,

[16]

it is often skipped and

underappreciated by physicians due to insufficient

awareness of its value as a marker of cardiovascular

risk.

[9]

There is considerable uncertainty

concern-ing the prevalence of

MAU among

hyper-tensive patients, the

reported rates varying

from as low as 4%

[17]

to

as high as 40%

[18]

and even to 70%.

[9]

Considering the potential role of baseline

albumin-uria in predicting subsequent risk levels for

cardiovas-cular complications in patients with essential

hyper-tension,

[5]

the present study was designed to evaluate

the prevalence of MAU and associated cardiovascular

risk factors among hypertensive patients.

Study population

The multinational observational study called

i-SEARCH was conducted in 26 countries around the

world including 21,050 patients.

[9]

Of these, 1,926

hy-pertensive patients from different centers of Turkey

composed the Turkish arm and were surveyed in an

observational and cross-sectional design aiming to

de-termine the prevalence of MAU and the risk factors

associated with MAU. Over a 6-month study period,

the study population initially consisted of 2,066

tients presenting to medical centers. Of these, 2032

pa-tients gave written informed consent to participate in

the study. After exclusion of 106 patients who failed to

meet inclusion criteria or had missing entries in their

Case Report Form with respect to cardiovascular

his-tory or albumin and creatinine levels, the remaining

1,926 patients constituted the final population. Ethics

committee approvals for the study were obtained from

all participating centers. The study was conducted in

accordance with the ethical principles of the current

Declaration of Helsinki and with the standards of the

International Conference on Harmonization/Good

Clinical Practice.

The sample was composed of male and female

outpatients, aged 18 years or older, currently under

treatment of or with newly diagnosed essential

arte-rial hypertension, defined as a seated systolic/diastolic

blood pressure of >140/90 mmHg measured at rest

during a single clinical visit. Exclusion criteria were

the presence of the following: acute fever (>38 °C),

re-nal disease (serum creatinine >20 mg/l), concomitant

urinary tract infection, cimetidine therapy, pregnancy,

menstrual bleeding and, in order to prevent

false-pos-itive results, strenuous physical activity in the

preced-ing 24 hours.

PATIENTS AND METHODS

Abbreviations:

ACE Angiotensin-converting enzyme CAD Coronary artery disease MAU Microalbuminuria

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Study design and procedures

The study protocol included assessment of data

de-rived from the Case Report Form of each patient,

in-cluding demographic features, body mass index (kg/

m

2

), waist circumference (cm), waist/hip ratio, vital

signs (blood pressure, pulse pressure, heart rate),

uri-nary albumin excretion, cardiovascular history,

car-diovascular risk factors, comorbidities, symptoms and

signs of cardiovascular disease, and current chronic

drug therapy. Urinary albumin excretion was

de-termined with a standardized sample collection and

urinary dipstick screening test for MAU using the

re-agent strips provided by the sponsor (Microalbustix,

Bayer Leverkusen, Germany), which have a

sensitiv-ity of 82.6%.

[19]

Possible urine albumin levels were 10,

30, 80 or 150 mg/l. Levels of cholesterol, triglyceride,

high-density lipoprotein cholesterol, low-density

li-poprotein cholesterol, C-reactive protein, and serum

creatinine were recorded, if they had been assessed

within the past 12 months. The Sokolow index, used

to assess the presence of left ventricular hypertrophy,

calculated from the last available electrocardiogram,

and left ventricular function (ejection fraction) were

also included in each patient’s Case Report Form.

Statistical analysis

Data on population characteristics for demographic

features, past history of hypertension, comorbidities,

and current treatment were summarized into counts of

nonmissing data and shown as mean±standard

devia-tion or percent where appropriate. Subgroup

compari-sons were done by the chi-square test and Student’s

t-test according to the characteristics of data.

Characteristics of the study population are summarized

in Table 1. The mean age was 56.9±11.4 years, and

41.1% of the subjects were aged 60 years or beyond.

Females accounted for 56.9%. The mean body mass

in-dex was 29.6±5.1 kg/m

2

and 40.7% of the patients had

clinical obesity with a body mass index of 30 kg/m

2

or greater. Almost two-thirds of the patients (67.5%)

had an abnormally high waist circumference

exceed-ing 88 cm in women and 102 cm in men; and the mean

waist/hip ratio was 0.9±0.1. The majority of the patients

(82.5%) were found to have uncontrolled hypertension.

The mean duration of hypertension was 7±6.3 years and

almost one-third of the population was hypertensive for

≥10 years. Systolic and diastolic blood pressures were

153.1±21.9 mmHg and 91.8±11.9, respectively, with a

RESULTS

Table 1. Demographic features, vital signs, and past history of hypertension in the study population

n % Mean±SD

Age (years) 56.9±11.4

Gender 1913

Male 825 43.1

Female 1088 56.9

Body mass index (kg/m2) 1899 29.6±5.1

<18 kg/m2 3 0.2 18 to <25 kg/m2 289 15.2 25 to <28 kg/m2 497 26.2 28 to <30 kg/m2 337 17.8 30 to <35 kg/m2 518 27.3 ≥35 kg/m2 255 13.4 Waist circumference* 1874 100.5±13.9 Normal 610 32.6 Abnormal 1264 67.5

Waist / hip ratio 0.9±0.1

Hypertension Duration (years) 1736 7.0±6.3 <5 years 729 42.0 5 to <10 years 458 26.4 ≥10 years 549 31.6 Hypertension control** 1926 Yes 337 17.5 No 1589 82.5 Vital signs

Systolic blood pressure (mmHg) 1922 153.1±21.9

<120 mmHg 55 2.9 120 to <130 mmHg 125 6.5 130 to <140 mmHg 209 10.9 140 to <160 mmHg 721 37.5 160 to <180 mmHg 527 27.4 ≥180 mmHg 285 14.8

Diastolic blood pressure (mmHg) 1922 91.8±11.9

<80 mmHg 154 8.0 80 to <85 mmHg 333 17.3 85 to <90 mmHg 88 4.6 90 to <100 mmHg 650 33.8 100 to <110 mmHg 511 26.6 ≥110 mmHg 186 9.7 Pulse pressure (mmHg) 61.2±16.1 Heart rate (bpm) 78.2±11.2 Sinus rhythm 1866 96.9

*Waist circumference was considered normal for <102 cm (men) and <88 cm (women); abnormal for ≥102 cm (men) and ≥88 cm (women). **Blood pressure was considered to be uncontrolled if systolic blood pressure was ≥140 mmHg and/or diastolic blood pressure was ≥90 mmHg.

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mean pulse pressure of 61.2±16.1 mmHg. The mean

heart rate was 78.2±11.2 bpm (Table 1).

Concerning cardiovascular risk factors, 35.6% had

dyslipidemia and 35.5% had diabetes,

predominant-ly type 2 (Table 2). Nearpredominant-ly one-third of the patients

(26.4%) had evidence for cardiovascular-related

co-morbidities, with 20.3% having documented coronary

artery disease. Almost all patients (96.8%) had one or

more risk factors for cardiovascular disease in

addi-tion to hypertension, which included history of

myo-cardial infarction or CAD, diabetes, dyslipidemia, lack

of physical exercise, or history of smoking (Table 2).

The majority of the patients (86.3%) were

pre-scribed cardiovascular medications, while 55% were

also on a special diet for cardiovascular disease risk

reduction. Most commonly prescribed drugs were

antiplatelet/anticoagulant agents (53.8%),

angiotensin-converting enzyme inhibitors (40.9%) and

beta-block-ers (36.1%) as antihypertensives, and lipid-lowering

agents (34.8%) (Table 3). Statins were the most widely

prescribed lipid-lowering drugs, with 32.6% of the

pa-tients. Among the subgroup of patients with

hyperten-sion and concomitant diabetes, 42.2% of patients were

receiving oral hypoglycemic drugs and/or insulin.

Prevalence of microalbuminuria

Among the study population, relatively few patients

had impaired renal function. Only 1.9% had

previ-ously known albuminuria; however, urinalysis with

a one-time dipstick test revealed that 64.7% of the

study population had evidence for MAU, with similar

prevalence rates in women (64.4%) and men (65%)

(Table 2). Gender did not have any influence on the

prevalence of MAU and waist circumference did not

differ significantly between patients with and without

MAU (Table 2). There was also no difference with

respect to beta-blocker, ACE inhibitor, and

angioten-sin-receptor blocker use between patients with and

without MAU. Beta-blockers, angiotensin-receptor

blockers and ACE inhibitors were prescribed in 235

(34.6%), 198 (29.1%) and 270 (39.7%) patients

with-out MAU compared to 461 (37.0%), 350 (28.1%), and

517 (41.5%) patients with MAU, respectively. The

prevalences of MAU with respect to varying levels

urinary albumin excretion and the presence of CAD

are shown in Figure 1.

Microalbuminuria has been associated with an

in-creased risk for renal and cardiovascular morbidity

Table 2. The prevalences of microalbuminuria, cardiovascular risk factors, and comorbidities

n % Mean±SD Microalbuminuria 1926 Present 1246 64.7 Absent 680 35.3 Male (n=825) Present 536 65.0 Absent 289 35.0 Female (n=1088) Present 701 64.4 Absent 387 35.6 Waist circumference (cm) Present (n=1214) 100.8±13.4 Absent (n=673) 100.1±14.8

Risk factors for cardiovascular disease At least one risk factor

Present 1864 96.8

Absent 62 3.2

Family history of MI / CAD 591 30.7 Lack of regular physical exercise 1550 80.5 Smoking

Current 389 20.2

Former 264 13.7

Additional risk factors

Total cholesterol (mmol/l) 5.3±1.3 HDL cholesterol (mmol/l) 1.3±0.5 LDL cholesterol (mmol/l) 3.2±1.0

Triglycerides (mmol/l) 1.8±1.1

C-reactive protein (mg/dl) 0.9±1.0 Duration of diabetes (years) 7.6±8.3 Current diabetics 670 35.5

Type 1 diabetes 20 5.6

Type 2 diabetes 338 94.4

Creatinine clearance (ml/min) 1431 99.7±36.9

<30 ml/min 5 0.4 30 to <60 ml/min 152 10.6 60 to <80 ml/min 282 19.7 80 to <120 ml/min 648 45.3 ≥120 ml/min 344 24.0 Comorbidities (n=1926)

At least one comorbidity 508 26.4 Coronary artery disease 390 20.3 Congestive heart failure 86 4.5 Atrial fibrillation 75 3.9 History of ischemic stroke 54 2.8 History of transient ischemic attack 38 2.0 Peripheral artery disease 23 1.2

Overall 15 0.8

Endarterectomy 6 42.9

MI: Myocardial infarction; CAD: Coronary artery disease; *At least one additional cardiovascular risk represents one of the following: family history of MI or documented CAD, lack of regular physical exercise, current or former smoking, known hyperlipidemia, or diabetes mellitus.

DISCUSSION

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and all-cause mortality in diabetic and/or

hyperten-sive patients and in elderly subjects.

[5]

Microalbuminuria was found in 64.7% of the

screened population in our study, which was in

accor-dance with the upper limits of prevalence rates defined

in published studies.

[9,17,18]

In fact, the high prevalence

of MAU determined in some countries, as well as in

Turkey, within the entire i-SEARCH survey has been

related to involvement of patients with diabetes, CAD,

and albuminuria unlike their exclusion in past studies.

[9]

Moreover, inclusion of all three grades of

hyperten-sion according to the European Society of

Hyperten-sion-European Society of Cardiology (ESC/ESH) 2003

guidelines

[16]

in the i-SEARCH survey was also stated

to be responsible for the observation of high MAU

prevalence.

[9]

Nonetheless, the finding of such a high

MAU prevalence among hypertensive patients seems

to be significant owing to well-known long-term

det-rimental effects of MAU on the cardiovascular system.

Besides our findings on lack of regular physical

ac-tivity, dyslipidemia, prominent risk factors, and

con-comitant diseases such as diabetes, congestive heart

failure, and CAD, atrial fibrillation was a remarkable

accompaniment for MAU. Of 75 patients with atrial

fibrillation, 59 (78.7%) had MAU.

This was compatible with the results of the LIFE

study,

[8]

in which a 4- to 5-fold increase in risk for

car-diovascular events was observed in the presence of

high albumin excretion rates, suggesting an

associa-tion with cardiac organ damage.

On the other hand, unlike the overall results of the

i-SEARCH survey showing a higher risk for MAU

among males with higher waist circumference

val-ues,

[9]

there was no gender influence on the risk for

MAU in our population, nor any association with

waist circumference.

Our results were in accordance with the

well-known interaction between the MAU level and

ac-companying CAD, which was also supported by

ob-servations from the HOPE study,

[11]

reporting a close

relationship between MAU and the cardio-renal risk.

The prevalence of MAU (50%) detected among

dia-betic hypertensive patients in the present study was

similar to that obtained in the DEMAND study,

[20]

in which albuminuria was not an exclusion

crite-ria and not all the diabetics were hypertensive. In

fact, blood pressure-lowering in type 2 diabetes was

shown to have a remarkable cardiovascular

protec-tive effect regardless of the drug(s) used, leading to

an assumption that cardiovascular benefit in diabetes

may mainly originate from lowering blood pressure

per se.

[21,22]

Concerning the role of drug treatment,

prescrip-tion of cardiovascular and antidiabetic drugs

includ-Table 3. Past and present history of medical

treatment for cardiovascular disease

Drugs n % Thiazide diuretics 461 23.9 Aldosterone antagonists 37 1.9 Loop diuretics 52 2.7 Calcium-channel blockers 445 23.1 Beta-blockers 696 36.1 Alpha-blockers 52 2.7 Angiotensin-receptor blockers 548 28.5 Angiotensin-converting enzyme inhibitors 787 40.9

Lipid-lowering agents 671 34.8

Statins 627 32.6

Fibrates 63 3.3

Antiplatelet / anticoagulant agent 1037 53.8

Aspirin 1017 52.8 Warfarin 37 1.9 0 10 20 30 40 10 mg/dl (n=680) 30 mg/dl(n=741) 80 mg/dl(n=267) 150 mg/dl(n=238) without coronary artery disease Urinary albumin excretion rate in patients

with coronary artery disease 36.5 38.637.6 13.2 16.2 11.5 15.6 30.5 Frequency of microalbuminuria (%)

Figure 1. Prevalence of microalbuminuria in the study population with respect to different levels urinary albumin excretion and the presence of coronary artery disease.

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ing calcium-channel blockers, thiazides, aldosterone

antagonists, loop diuretics, alpha-blockers, digitalis,

oral nitrates, antiarythmic drugs, biguanides,

sulfonyl-ureas, insulin, and anticoagulants including warfarin/

Coumadin was shown to be associated with increased

risk for MAU.

[9]

However, there was no significant

association between MAU risk and the use of ACE

inhibitors, angiotensin receptor antagonists, and

beta-blockers in the present study, indicating the

impor-tance of normalization of MAU as a therapeutic goal

in reducing cardiovascular risk besides achieving tight

blood pressure control.

[9]

In fact, evidence from the IRMA-2,

[23]

IDNT,

[24]

and LIFE

[8]

studies suggested that beta-blockers,

ACE inhibitors, and calcium-channel blockers

were all associated with increased risk for MAU.

The limited efficacy of drugs in preventing diabetic

nephropathy accompanying cardiovascular disease

has been reported to mandate use of

renin-angioten-sin system-blocking agents.

[9]

Therefore, failure of

such drugs to effectively reduce MAU was accused

for the related increase in MAU risk. Therefore, our

results contradictory to the past studies in terms of

MAU risk reduction obtained via beta-blockers and

ACE inhibitors may indicate the successful

man-agement of the underlying conditions targeted with

these drugs as far as our study population is

con-cerned.

Supporting the lack of MAU risk related with the

use of ACE inhibitors, they were recommended as

pri-mary preventive intervention against nephropathy

[25]

based on recent evidence concerning prevention of

MAU with ACE inhibition.

[26]

Angiotensin receptor

antagonists such as irbesartan have been considered

to be the first-line therapy in all major guidelines and

are especially recommended in patients with diabetic

nephropathy.

[27]

Even though hypertension-associated diseases are

still the leading cause of death, poor blood pressure

control is evident in more than 70% of hypertensive

patients worldwide.

[28]

In this respect, while the vast

majority of the patients in the present study were

receiving treatment for hypertension, the detection

of poor blood pressure control over three-quarters

of the study population seems notable in terms of

high rates of MAU, in line to data obtained from the

i-SEARCH study. In this context, since benefits of

treating hypertension are not fully attained until a

patient has been treated for 4 to 5 years,

[29]

aggressive

blood pressure lowering has been considered to be

essential in reducing cardiovascular morbidity and

mortality in the hypertension in relation to leading to

appropriate reductions in MAU and associated

car-diovascular risk.

[8,9,30]

In conclusion, we propose that MAU has a high

prevalence rate among hypertensive outpatients with

cardiovascular risk factors and/or concomitant CAD

or diabetes. Being an early and independent

modifi-able risk marker responsive to antihypertensive

medi-cation, MAU should be routinely used as a screening

and monitoring tool in the assessment of subsequent

cardiovascular morbidity and mortality in

hyperten-sive patients.

Limitations

Although the use of a standardized procedure for

de-termining MAU in all participating centers increases

the possibility of a reliable interpretation of our

re-sults, the measurement of MAU on a single occasion

comprises the main limitation to the present study and

contradicts the international guidelines

recommend-ing triple testrecommend-ing.

[9]

However, data obtained in the

NHANES III survey

[31]

indicate that at least 65% of

patients with a positive test will also test positive on a

subsequent occasion.

Acknowledgments

This study was funded by a research grant from

Sano-fi-Aventis. There are no conflict of interest issues for

any of the authors, nor for the results.

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Key words: Albuminuria/complications/epidemiology; cardiovas-cular diseases; coronary artery disease; hypertension/complica-tions; prevalence; risk factors; Turkey/epidemiology.

Anah tar söz cük ler: Albuminüri/komplikasyon/epidemiyoloji; kardi-yovasküler hastalık; koroner arter hastalığı; hipertansiyon/kompli-kasyon; prevalans; risk faktörü; Türkiye/epidemiyoloji.

Appendix. Complete list of the investigators participating in the Turkish arm of the i-SEARCH study and their affiliations (by alphabetical order):

Author Affiliation

1. A. Halim Sözcüer, M.D. Merkez Efendi State Hospital, Cardiology Clinic, Manisa 2. Abdulkadir Kerpeten, M.D. Kütahya State Hospital, Cardiology Clinic, Kütahya 3. Abdullah Delice, M.D. Kızılay Health Center, Cardiology Polyclinic, Kayseri 4. Abdullah İçli, M.D. Konya Municipality Hospital, Cardiology Clinic, Konya

5. Abdullah Sökmen, M.D. Sütçü İmam University Medical Faculty, Department of Cardiology, Kahramanmaraş 6. Adalet Gürlek, M.D. Ankara University Medical Faculty, Department of Cardiology, İbn-i Sina Hospital, Ankara 7. Adnan Abacı, M.D. Gazi University Medical Faculty, Department of Cardiology, Ankara

8. Adnan Bayram, M.D. Erzurum Numune State Hospital, Cardiology Clinic, Erzurum 9. Adnan Köşüş, M.D. Ordu Medical Center, 19 Eylül Internal Diseases Polyclinic, Ordu 10. Ahmet Çamsarı, M.D. Mersin University Medical Faculty, Department of Cardiology, Mersin 11. Ahmet Sakallı, M.D. Afyon State Hospital, Cardiology Clinic, Afyon

12. Ahmet Sert, M.D. Beypazarı State Hospital, Cardiology Clinic, Ankara

13. Ahmet Temizhan, M.D. Ankara Yüksek İhtisas Training and Research Hospital, Cardiology Clinic, Ankara 14. Ahmet Yılmaz, M.D. Cumhuriyet University Medical Faculty, Department of Cardiology, Sivas

15. Aldunay Daver, M.D. Antalya State Hospital, Cardiology Clinic, Antalya

16. Ali Aydınlar, M.D. Uludağ University Medical Faculty, Department of Cardiology, Bursa 17. Ali Ergin, M.D. Erciyes University Medical Faculty, Department of Cardiology, Kayseri 18. Ali Erhan Kılıçoğlu, M.D. Elazığ State Hospital, Cardiology Clinic, Elazığ

19. Alparslan Birdane, M.D. Osmangazi University Medical Faculty, Department of Cardiology, Eskişehir 20. Alpay Arıbaş, M.D. Konya Numune State Hospital, Cardiology Clinic, Konya

21. Aret Lazoğlu, M.D. Intermed Medical Center, Cardiology Clinic, Alanya, Antalya 22. Aslan Özdemir, M.D. 1 Eylül State Hospital, Cardiology Clinic, Uşak

23. Aşkın Fiskeci, M.D. Balıkesir State Hospital, Cardiology Clinic, Balıkesir

24. Ataç Çelik, M.D. Afyon Kocatepe University Medical Faculty, Department of Cardiology, Afyon 25. Atilla Bitigen, M.D. Kartal Koşuyolu Training and Research Hospital, Cardiology Clinic, İstanbul 26. Atilla Keskin, M.D. Akhisar State Hospital, Cardiology Clinic, Manisa

27. Atilla Yavuz, M.D. Kartal Koşuyolu Training and Research Hospital, Cardiology Clinic, İstanbul 28. Aydın Akyüz, M.D. Sultan 1. İzzettin Keykavuş State Hospital, Cardiology Clinic, Sivas 29. Aydın Karanfil, M.D. Fatih University Medical Faculty, Department of Cardiology, Ankara 30. Aydın Ünsal, M.D. Gölcük State Hospital, Cardiology Clinic, Kocaeli

31. Ayhan Sinci, M.D. Bilecik State Hospital, Cardiology Clinic, Bilecik 32. Ayşe Uğur Gülmez, M.D. Pamukkale State Hospital, Cardiology Clinic, Denizli

33. Ayşegül Irmak, M.D. Ankara Training and Research Hospital, Cardiology Clinic, Ankara 34. Aytaç Vural, M.D. Toros State Hospital, Cardiology Clinic, Mersin

35. Aytekin Güven, M.D. Sütçü İmam University Medical Faculty, Department of Cardiology, Kahramanmaraş 36. Barış İlerigelen, M.D. İstanbul University Cerrahpaşa Medical Faculty, Department of Cardiology, İstanbul 37. Bekir Erol, M.D. Giresun State Hospital, Cardiology Clinic, Giresun

38. Bülent Polat, M.D. Polatlı Duatepe State Hospital, Cardiology Clinic, Ankara 39. Bülent Tosun, M.D. Aydın 82. Yıl State Hospital, Cardiology Clinic, Aydın 40. Cahit Ağçal, M.D. Isparta State Hospital, Cardiology Clinic, Isparta

41. Celal Genç, M.D. Gülhane Military Medical Academy, Department of Cardiology, Ankara 42. Celal Kırdar, M.D. Eskişehir State Hospital, Cardiology Clinic, Eskişehir

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44. Cem Köz, M.D. Gülhane Military Medical Academy, Department of Cardiology, Ankara 45. Cem Nazlı, M.D. Atatürk Training and Research Hospital, Cardiology Clinic, İzmir

46. Ceyhun Ceyhan, M.D. Adnan Menderes University Medical Faculty, Department of Cardiology, Aydın 47. Cihan Örem, M.D. Karadeniz Technical University Medical Faculty, Department of Cardiology, Trabzon 48. Cihangir Uyan, M.D. Abant İzzet Baysal University Medical Faculty, Department of Cardiology, Bolu 49. Cüneyt Türkoğlu, M.D. Ege University Medical Faculty, Department of Cardiology, İzmir

50. Daryuş Gaffari, M.D. Kızılay Health Center, Cardiology Polyclinic, Üsküdar, İstanbul 51. Deniz Aytekin, M.D. Salihli Public Hospital, Cardiology Clinic, Manisa

52. Dilek Ural, M.D. Kocaeli University Medical Faculty, Department of Cardiology, Kocaeli 53. Dilek Yeşilbursa, M.D. Uludağ University Medical Faculty, Department of Cardiology, Bursa

54. Dursun Aras, M.D. Ankara Yüksek İhtisas Training and Research Hospital, Cardiology Clinic, Ankara 55. Ender Semiz, M.D. Pamukkale University Medical Faculty, Department of Cardiology, Denizli 56. Enis Koçak, M.D. Evliya Çelebi State Hospital, Cardiology Clinic, Kütahya

57. Enver Atalar, M.D. Hacettepe University Medical Faculty, Department of Cardiology, Ankara 58. Ercan Varol, M.D. Süleyman Demirel University Medical Faculty, Department of Cardiology, Isparta 59. Ersel Onrat, M.D. Afyon Kocatepe University Medical Faculty, Department of Cardiology: Afyon 60. Ertuğrul Şensoy, M.D. Ankara Training and Research Hospital, Cardiology Clinic, Ankara

61. Esmeray Acartürk, M.D. Çukurova University Medical Faculty, Department of Cardiology, Adana 62. Eyüp Akarca, M.D. Nazilli State Hospital, Cardiology Clinic, Aydın

63. Eyüp Aygün, M.D. Bafra State Hospital, Cardiology Clinic, Samsun

64. Fatih Sinan Ertaş, M.D. Ankara University Medical Faculty, Department of Cardiology, Ankara 65. Feray Koca, M.D. Alsancak State Hospital, Cardiology Clinic, İzmir

66. Ferhan Özmen, M.D. Hacettepe University Medical Faculty, Department of Cardiology, Ankara 67. Feridun Vasfi Ulusoy, M.D. Ankara Numune Hospital, 2nd Cardiology Clinic, Ankara

68. Filiz Özerkan, M.D. Ege University Medical Faculty, Department of Cardiology, İzmir 69. Füsun Kara İnceer, M.D. Çorum State Hospital, Cardiology Clinic, Çorum

70. Giray Kabakcı, M.D. Hacettepe University Medical Faculty, Department of Cardiology, Ankara

71. Güçlü Dönmez, M.D. Bakırköy Dr. Sadi Konuk Training and Research Hospital, Department of Cardiology, İstanbul 72. Gülden Topkara, M.D. Bandırma State Hospital, Cardiology Clinic, Balıkesir

73. Gülsüm Daş, M.D. 82. Yıl State Hospital, Cardiology Clinic, Adıyaman 74. Hakan Bozkurt, M.D. Antakya State Hospital, Cardiology Clinic, Antakya

75. Hakan Kültürsay, M.D. Ege University Medical Faculty, Department of Cardiology, İzmir

76. Hakan Tıkız, M.D. Celal Bayar University Medical Faculty, Department of Cardiology, Manisa 77. Haldun Akgöz, M.D. Siyami Ersek Hospital, Cardiology Clinic, İstanbul

78. Halil Kaymak, M.D. Tarsus State Hospital, Cardiology Clinic, Mersin 79. Halim Öney, M.D. Artvin State Hospital, Cardiology Clinic, Artvin 80. Haluk Yeğin, M.D. Antalya State Hospital, Cardiology Clinic, Antalya

81. Hasan Boğa, M.D. Adana Numune Training and Research Hospital, Fatma Timurçin Heart Center, Adana 82. Hasan Gök, M.D. Selçuk State Hospital, Cardiology Clinic, İzmir

83. Hasan Vural, M.D. Vedat Ali Özkan State Hospital, Cardiology Clinic, Kayseri 84. Hüsamettin Atasever, M.D. Adapazarı State Hospital, Cardiology Clinic, Adapazarı

85. Hüseyin Arınç, M.D. İzzet Baysal University Medical Faculty, Department of Cardiology, Düzce 86. Hüseyin Bozdemir, M.D. Buca Seyfi Demirsoy State Hospital, Cardiology Clinic, İzmir

87. Hüseyin Gündüz, M.D. İzzet Baysal University Medical Faculty, Department of Cardiology, Düzce 88. Hüseyin Tunar, M.D. Salihli State Hospital, Cardiology Clinic, Manisa

89. Hüsnü Atmaca, M.D. Siyami Ersek Hospital, Cardiology Clinic, İstanbul 90. İbrahim Doğru, M.D. Çukurova State Hospital, Cardiology Clinic, Adana

91. İbrahim Özdoğru, M.D. Erciyes University Medical Faculty, Department of Cardiology, Kayseri 92. İbrahim Susal, M.D. Karşıyaka State Hospital, Cardiology Clinic, İzmir

93. İpek Türkoğlu Kurt, M.D. Atakalp Heart Hospital, Cardiology Clinic, İzmir

94. İrem Dinçer, M.D. Ankara University Medical Faculty, Department of Cardiology, Ankara 95. İsmail Bıyık, M.D. Uşak State Hospital, Cardiology Clinic, Uşak

96. İzzet Tandoğan, M.D. Cumhuriyet University Medical Faculty, Department of Cardiology, Sivas 97. Jale Jordan, M.D. Uludağ University Medical Faculty, Department of Cardiology, Bursa 98. Kaan Kulan, M.D. Trabzon Numune State Hospital, Cardiology Clinic, Trabzon 99. Kadir Şahna, M.D. Ordu State Hospital, Cardiology Clinic, Ordu

100. Kamuran Öztaş, M.D. Samsun State Hospital, Cardiology Clinic, Samsun 101. Kenan Dönmez, M.D. Manavgat State Hospital, Cardiology Clinic, Antalya

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103. Kubilay Kaya, M.D. Bursa State Hospital, Cardiology Clinic, Bursa

104. Kudret Aytemir, M.D. Hacettepe University Medical Faculty, Department of Cardiology, Ankara 105. Kurtuluş Özdemir, M.D. Selçuk University Medical Faculty, Department of Cardiology, Konya 106. Kürşat Tigen, M.D. Ümraniye State Hospital, Cardiology Clinic, İstanbul

107. Levent Saraç, M.D. İstinye State Hospital, Cardiology Clinic, İstanbul 108. M. Tarık Sirkeci, M.D. Kızılay Health Center, Cardiology Polyclinic, Erzincan 109. Mahmut Çakmak, M.D. Ümraniye State Hospital, Cardiology Clinic, İstanbul

110. Mahmut Şahin, M.D. Ondokuz Mayıs University Medical Faculty, Department of Cardiology, Samsun 111. Makbule Kutlu, M.D. Harput State Hospital, Cardiology Clinic, Elazığ

112. Mehmet Bilge, M.D. Ankara Atatürk Training and Research Hospital, Cardiology Clinic, Ankara 113. Mehmet Bostan, M.D. Rize State Hospital, Cardiology Clinic, Rize

114. Mehmet Melek, M.D. Afyon Kocatepe University Medical Faculty, Department of Cardiology: Afyon 115. Mehmet Ömrü Sunay, M.D. Balıkesir State Hospital, Cardiology Clinic, Balıkesir

116. Mehmet Şeker, M.D. Meram State Hospital, Cardiology Clinic, Konya

117. Mehmet Şükrü Güçel, M.D. Adana Numune Training and Research Hospital, Fatma Timurçin Heart Center, Adana 118. Mehmet Yazıcı, M.D. Düzce University Medical Faculty, Department of Cardiology, Düzce

119. Meral Kayıkçıoğlu, M.D. Ege University Medical Faculty, Department of Cardiology, İzmir 120. Mete Öç, M.D. Ümraniye State Hospital, Cardiology Clinic, İstanbul

121. Metin Gürsürer, M.D. Karaelmas University Medical Faculty, Department of Cardiology, Zonguldak 122. Muammer Dağalp, M.D. Ziraat Bank Hospital, Cardiology Clinic, Ankara

123. Murat Bilaloğlu, M.D. Erzurum Numune State Hospital, Cardiology Clinic, Erzurum

124. Murat Yalçın, M.D. GATA Haydarpaşa Training and Research Hospital, Department of Cardiology, İstanbul 125. Murteza Şerifi, M.D. İzmit State Hospital, Cardiology Clinic, Kocaeli

126. Mustafa Gökçe, M.D. Karadeniz Technical University Medical Faculty, Department of Cardiology, Trabzon 127. Mustafa Kılıçkap, M.D. Ankara University Medical Faculty, Department of Cardiology, The Heart Center, Ankara 128. Mustafa Polat, M.D. Ceyhan State Hospital, Cardiology Clinic, Adana

129. Mustafa Şan, M.D. Çukurova University Medical Faculty, Department of Cardiology, Adana 130. Mustafa Tahtasız, M.D. Eşrefpaşa Municipality Hospital, Cardiology Clinic, İzmir

131. Muzaffer Yılmaz, M.D. Kayseri State Hospital, Cardiology Clinic, Kayseri

132. Mümin Etemoğlu, M.D. İzmir Training and Research Hospital, Cardiology Clinic, İzmir 133. Naci Coşkun, M.D. Harput State Hospital, Cardiology Clinic, Elazığ

134. Nazif Sinan Aran, M.D. İstanbul University Cerrahpaşa Medical Faculty, Department of Cardiology, İstanbul 135. Necmi Ata, M.D. Osmangazi University Medical Faculty, Department of Cardiology, Eskişehir 136. Nejat Sönmez, M.D. Bodrum State Hospital, Cardiology Clinic, Muğla

137. Neşe Çam, M.D. Siyami Ersek Hospital, Cardiology Clinic, İstanbul

138. Nevres Koylan, M.D. İstanbul University İstanbul Medical Faculty, Department of Cardiology, İstanbul 139. Nihat Özer, M.D. İskenderun State Hospital, Cardiology Clinic, Hatay

140. Nurgül Keser, M.D. Maltepe University Medical Faculty, Department of Cardiology, İstanbul 141. Oben Döven, M.D. Mersin University Medical Faculty, Department of Cardiology, Mersin 142. Okan Tartanoğlu, M.D. Karaman State Hospital, Cardiology Clinic, Karaman

143. Oktay Ergene, M.D. Atatürk Training and Research Hospital, Cardiology Clinic, İzmir 144. Oktay Sancaktar, M.D. Akdeniz University Medical Faculty, Department of Cardiology, Antalya 145. Orhan Hakan Elönü, M.D. Melikgazi Hospital, Cardiology Clinic, Kayseri

146. Osman Alper Onbaşılı, M.D. Adnan Menderes University Medical Faculty, Department of Cardiology, Aydın 147. Ömer Kozan, M.D. Dokuz Eylül University Medical Faculty, Department of Cardiology, İzmir 148. Özlem Özbek, M.D. Marmara University Medical Faculty, Department of Cardiology, İstanbul 149. Pelin Pınar, M.D. Manisa State Hospital, Cardiology Clinic, Manisa

150. Ramazan Akdemir, M.D. Düzce University Medical Faculty, Department of Cardiology, Düzce 151. Ramazan Kargın, M.D. Kartal Koşuyolu Training and Research Hospital, Cardiology Clinic, İstanbul 152. Ramazan Topsakal, M.D. Erciyes University Medical Faculty, Department of Cardiology, Kayseri 153. Recep Yoldaş, M.D. Konya Numune State Hospital, Cardiology Clinic, Konya

154. Rıdvan Uçar, M.D. Giresun State Hospital, Cardiology Clinic, Giresun

155. Sabahattin Ateşal, M.D. Atatürk University Medical Faculty, Department of Cardiology, Erzurum

156. Sabahattin Toktaş, M.D. Adana Numune Training and Research Hospital, Fatma Timurçin Heart Center, Adana 157. Sacit Cinsoy, M.D. Sabuncuoğlu Şerafeddin State Hospital, Cardiology Clinic, Amasya

158. Sadi Güleç, M.D. Ankara University Medical Faculty, Department of Cardiology, Ankara 159. Saide Aytekin, M.D. Kadir Has University Medical Faculty, Department of Cardiology, İstanbul 160. Salih Çolak, M.D. Kızılay Health Center, Cardiology Polyclinic, Sivas

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162. Sedat Sakallı, M.D. Siyami Ersek Hospital, Cardiology Clinic, İstanbul

163. Serdar Sevimli, M.D. Atatürk University Medical Faculty, Department of Cardiology, Erzurum

164. Serkan Topaloğlu, M.D. Ankara Yüksek İhtisas Training and Research Hospital, Cardiology Clinic, Ankara 165. Sinan Aydoğdu, M.D. Ankara Numune Hospital, Cardiology Clinic, Ankara

166. Sinan Coşku Turan, M.D. Fatih Sultan Mehmet State Hospital, Cardiology Clinic, İstanbul 167. Sinan Kahraman, M.D. Niğde State Hospital, Cardiology Clinic, Niğde

168. Suat Yorgancı, M.D. Atatürk State Hospital, Cardiology Clinic, Antalya 169. Şenol Coşkun, M.D. Bursa State Hospital, Cardiology Clinic, Bursa 170. Şükrü Ünal, M.D. Nevşehir State Hospital, Cardiology Clinic, Nevşehir

171. Tahir Durmaz, M.D. Ankara Atatürk Training and Research Hospital, Cardiology Clinic, Ankara 172. Tahir Ulusoy, M.D. Aksaray State Hospital, Cardiology Clinic, Aksaray

173. Talat Keleş, M.D. Ankara Atatürk Training and Research Hospital, Cardiology Clinic, Ankara 174. Tamer Kırat, M.D. Muğla State Hospital, Cardiology Clinic, Muğla

175. Taner Turan Gündoğdu, M.D. Gebze Fatih Hospital, Cardiology Clinic, Kocaeli 176. Tezcan Peker, M.D. Gemlik State Hospital, Cardiology Clinic, Bursa

177. Umut Sümerkan, M.D. Marmara University Medical Faculty, Department of Cardiology, İstanbul 178. Vedat Aytekin, M.D. Kadir Has University Medical Faculty, Department of Cardiology, İstanbul 179. Vedat Koca, M.D. Bursa Yüksek İhtisas Training and Research Hospital, Cardiology Clinic, Bursa 180. Veday Çam, M.D. Fethiye State Hospital, Cardiology Clinic, Muğla

181. Veli Gökçe, M.D. Konya Numune State Hospital, Cardiology Clinic, Konya

182. Yekta Gürlertop, M.D. Atatürk University Medical Faculty, Department of Cardiology, Erzurum

183. Yücel Balbay, M.D. Ankara Yüksek İhtisas Training and Research Hospital, Cardiology Clinic, Ankara 184. Yüksel Çavuşoğlu, M.D. Osmangazi University Medical Faculty, Department of Cardiology, Eskişehir 185. Yusuf Erzurum, M.D. Eskişehir Yunus Emre State Hospital, Cardiology Clinic, Eskişehir

186. Yusuf Selçoki, M.D. Fatih University Medical Faculty, Department of Cardiology, Ankara 187. Yusuf Yakar, M.D. Tokat State Hospital, Cardiology Clinic, Tokat

188. Zafer Işılak, M.D. GATA Haydarpaşa Training and Research Hospital, Department of Cardiology, İstanbul 189. Zafer Tosun, M.D. Antalya State Hospital, Cardiology Clinic, Antalya

190. Zekeriya Kaplan, M.D. Ankara Training and Research Hospital, Cardiology Clinic, Ankara 191. Zeynep Tartan, M.D. Siyami Ersek Hospital, Cardiology Clinic, İstanbul

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